The proposed studies are designed to define the alterations in proximal tubular transport that occur when the number of functioning nephrons is reduced. Using micropuncture and microanalytic techniques in the rat, I will determine the relative contribution of changes in proximal sodium, chloride and bicarbonate reabsorption in maintaining extracellular fluid composition and volume in this model of renal insufficiency. These studies will be carried out for the first time in animals in which the surgically induced plasma losses are replaced to maintain volume status and renal function at levels seen in awake animals. The studies will also attempt to determine the factors responsible for alterations in proximal tubular transport; the relative roles of alterations in fluid and solute load via changes in single nephron GFR and of peritubular physical factors will be examined. The role of intrinsic changes in proximal tubular transport rates in response to chronic alterations in tubular load will be examined by microperfusion techniques. In addition, the kinetics of proximal bicarbonate reabsorption in the hypertrophied nephron will be defined. These studies should provide new insights into the nature of the adaptive response of the kidney to nephron loss.